Borrelia valaisiana Resist Complement-Mediated Killing Independently of the Recruitment of Immune Regulators and Inactivation of Complement Components

Abstract

Spirochetes belonging to the Borrelia (B.) burgdorferi sensu lato complex differ in their resistance to complement-mediated killing, particularly in regard to human serum. In the present study, we elucidate the serum and complement susceptibility of B. valaisiana, a genospecies with the potential to cause Lyme disease in Europe as well as in Asia. Among the investigated isolates, growth of ZWU3 Ny3 was not affected while growth of VS116 and Bv9 was strongly inhibited in the presence of 50% human serum. Analyzing complement activation, complement components C3, C4 and C6 were deposited on the surface of isolates VS116 and Bv9, and similarly the membrane attack complex was formed on their surface. In contrast, no surface-deposited components and no aberrations in cell morphology were detected for serum-resistant ZWU3 Ny3. While further investigating the protective role of bound complement regulators in mediating complement resistance, we discovered that none of the B. valaisiana isolates analyzed bound complement regulators Factor H, Factor H-like protein 1, C4b binding protein or C1 esterase inhibitor. In addition, B. valaisiana also lacked intrinsic proteolytic activity to degrade complement components C3, C3b, C4, C4b, and C5. Taken together, these findings suggest that certain B. valaisiana isolates differ in their capability to resist complement-mediating killing by human serum. The molecular mechanism utilized by B. valaisiana to inhibit bacteriolysis appears not to involve binding of the key host complement regulators of the alternative, classical, and lectin pathways as already known for serum-resistant Lyme disease or relapsing fever borreliae.

Early Cytokine Release in Response to Live Borrelia burgdorferi Sensu Lato Spirochetes Is Largely Complement Independent

“…One main finding regarding complement activation was the significant difference in found between the two strains of Borrelia . In accordance with previous findings [32] , we found that the complement-sensitive strain B. garinii LU59 induced a higher level of complement activation, as measured by the generation of C3a and sC5b-9 in plasma and detected by ELISA. Complement activation induced by the presence of Borrelia -specific antibodies resulted in a significant increase in generated sC5b-9, in agreement with other studies of the deposition of C5b-9 on the bacterial surface [8] , [18] , [33] , [34] .…”

“…In addition, low amounts of C4BP were detected on both strains, with a non-significantly higher level on B. garinii LU59. Binding of C4BP to B. garinii in the literature is contradictory, studies in which no binding of C4BP was detected when a similar experimental setup has been reported [13] , [32] as well as studies in line with data presented here where binding of C4BP is observed [15] .…”

BGA66 and BGA71 facilitate complement resistance of Borrelia bavariensis by inhibiting assembly of the membrane attack complex

“…Investigating degradation of different complement components (C1q, C3, C3b, C4, C5, C6, C7, C8 and C9), none of these molecules were enzymatically cleaved by spirochetes (Fig. F) concurrently confirming our previous observations obtained with B. burgdorferi , B. garinii and B. valaisiana , which also lacked any proteolytic activity for complement C3, C3b, C4, C4b and C5 (Schwab et al ., ).…”

Borrelia burgdorferi BBK32 Inhibits the Classical Pathway by Blocking Activation of the C1 Complement Complex

“…Interestingly, the Lyme disease spirochete B . valaisiana strain ZWU3 Ny3 was shown to possess a novel mechanism of complement inhibition independent of host complement regulator recruitment/mimicry [ 79 ]. Although a molecular mechanism has not been elucidated, the authors hypothesize that the inhibitory mechanism present in this strain of B .…”